Last updated: May 16, 2023

Summarytoggle arrow icon

Hypopituitarism refers to the inadequate production of one or more anterior pituitary hormones as a result of damage to the pituitary gland and/or hypothalamus. These hormones include growth hormone (GH), prolactin, thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). In some cases, the posterior pituitary hormones (e.g., ADH) may also be affected, which is known as panhypopituitarism. The most common cause of hypopituitarism is compression of the pituitary gland by a nonsecretory pituitary macroadenoma. Other common causes include postpartum pituitary necrosis (Sheehan syndrome), traumatic brain injury, hypophysectomy, and/or irradiation of the pituitary gland. Clinical manifestations vary significantly and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism: Growth hormone deficiency during childhood manifests with delayed growth, while prolactin deficiency in women can manifest as lactation failure. Deficiencies of other anterior pituitary hormones, on the other hand, manifest with clinical features of hypogonadotropic hypogonadism, secondary hypothyroidism, and/or secondary adrenal insufficiency (AI). Severe pituitary damage can also result in central diabetes insipidus as a result of ADH deficiency. Hypopituitarism is diagnosed by measuring specific hormone levels (depending on the underlying hormone deficiency) and with cranial imaging (in order to identify damage to the pituitary gland and/or hypothalamus). Treatment consists of hormone replacement therapy and treatment of the underlying disorder (e.g., transsphenoidal resection of pituitary adenomas).

Etiologytoggle arrow icon

Pathophysiologytoggle arrow icon

Clinical featurestoggle arrow icon

Symptoms are variable and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism.

Pituitary apoplexy, which results in acute hypocortisolism and hypothyroidism, can manifest with severe headache, sudden hypotension, and hypovolemic shock.

Diagnosticstoggle arrow icon

Approach [6]

Laboratory studies [6]

ACTH deficiency (central/secondary adrenal insufficiency) [7]

TSH deficiency (secondary hypothyroidism)

A normal TSH does not rule out secondary hypothyroidism; always send for serum free T4 levels.

LH/FSH deficiency (secondary hypogonadism)

The presence of regular menstrual cycles in women rules out hypogonadism.

Growth hormone deficiency

  • Testing is required if treatment is planned and optional if treatment is not planned and hormonal deficiencies exist in ≥ 3 pituitary axes.
  • IGF-1 level: typically ↓; may be normal [8]
  • Confirmatory testing: GH stimulation test [8][9]
    • Procedure
      • Record baseline serum GH level.
      • Administer stimulating agent (e.g., macimorelin).
      • Repeat serum GH levels at set intervals.
    • Interpretation: GH level (e.g., level < 2.8 mcg/L post macimorelin stimulation) supports a GH deficiency. [9]

Prolactin deficiency

  • Routine testing is not performed in the investigation of hypopituitarism.
  • Prolactin levels may be tested in:
  • Supportive finding: low-normal to low prolactin level, which does not increase with stimulation testing [10]

Posterior pituitary hormones: ADH deficiency (central diabetes insipidus)

Imaging [12]

Imaging of the pituitary is indicated in all patients to determine the underlying cause.

  • MRI brain
    • Preferred imaging modality
    • Findings depend on the underlying etiology and include pituitary adenomas (most common cause in adults), congenital malformations, and trauma.
  • CT Head (without IV contrast): used if there are contraindications to MRI or in patients requiring rapid evaluation, e.g., after suspected TBI or SAH

Treatmenttoggle arrow icon

Approach [6]

Emergency management

Acute loss of pituitary function, e.g., via pituitary apoplexy (including Sheehan syndrome), iatrogenic (hypophysectomy), or traumatic brain injury, can lead to life-threatening complications.

Patients with suspected adrenal crisis require immediate therapy with hydrocortisone.

Maintenance therapy for pituitary hormone deficiencies

Hormone replacement in hypopituitarism [6]
Secondary adrenal insufficiency
  • Routine management: glucocorticoids with dose increases during periods of stress
Secondary hypothyroidism
Secondary hypogonadism
Growth hormone deficiency [8]
  • Children: growth hormone replacement [16]
  • Adults: GH replacement may be offered but is not usually required.
Central diabetes insipidus

In addition to pituitary hormone replacement, the underlying cause of hypopituitarism should be treated.

Hypopituitarism patients with TSH deficiency should not be treated with levothyroxine until ACTH deficiency has been ruled out and/or treated because levothyroxine increases the clearance of cortisol and may precipitate an adrenal crisis.

Referencestoggle arrow icon

  1. Shivaprasad C. Sheehan's syndrome: Newer advances. Indian J Endocrinol Metab. 2011; 15 (Suppl 3): p.S203-207.doi: 10.4103/2230-8210.84869 . | Open in Read by QxMD
  2. Schrager S, Sabo L. Sheehan syndrome: a rare complication of postpartum hemorrhage. J Am Board Fam Pract. 2001; 14 (5): p.389-391.
  3. Halit Diri, Fatih Tanriverdi, Zuleyha Karaca, Serkan Senol, Kursad Unluhizarci, Ahmet Candan Durak, Hulusi Atmaca, Fahrettin Kelestimur. Extensive investigation of 114 patients with Sheehan's syndrome: a continuing disorder. European Journal of Endocrinology. 2014; 171 (3): p.311-318.doi: 10.1530/eje-14-0244 . | Open in Read by QxMD
  4. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2016; 101 (11): p.3888-3921.doi: 10.1210/jc.2016-2118 . | Open in Read by QxMD
  5. Struja T, Briner L, Meier A, et al. Diagnostic accuracy of basal cortisol level to predict adrenal insufficiency in cosyntropin testing: results from an observational cohort study with 804 patients. Endocr Pract. 2017; 23 (8): p.949-961.doi: 10.4158/ep171861.or . | Open in Read by QxMD
  6. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML. Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011; 96 (6): p.1587-1609.doi: 10.1210/jc.2011-0179 . | Open in Read by QxMD
  7. Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a Diagnostic Test for Adult GH Deficiency. The Journal of Clinical Endocrinology & Metabolism. 2018; 103 (8): p.3083-3093.doi: 10.1210/jc.2018-00665 . | Open in Read by QxMD
  8. Iwama S, Welt CK, Romero CJ, Radovick S, Caturegli P. Isolated Prolactin Deficiency Associated With Serum Autoantibodies Against Prolactin-Secreting Cells. The Journal of Clinical Endocrinology & Metabolism. 2013; 98 (10): p.3920-3925.doi: 10.1210/jc.2013-2411 . | Open in Read by QxMD
  9. Endotext. Updated: January 1, 2000. Accessed: November 3, 2020.
  10. Johnston PC, Hamrahian AH, Weil RJ, Kennedy L. Pituitary tumor apoplexy. Journal of Clinical Neuroscience. 2015; 22 (6): p.939-944.doi: 10.1016/j.jocn.2014.11.023 . | Open in Read by QxMD
  11. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014; 24 (12): p.1670-1751.doi: 10.1089/thy.2014.0028 . | Open in Read by QxMD
  12. Petering RC, Brooks NA. Testosterone Therapy: Review of Clinical Applications.. Am Fam Physician. 2017; 96 (7): p.441-449.
  13. Lee JA, Ramasamy R. Indications for the use of human chorionic gonadotropic hormone for the management of infertility in hypogonadal men.. Transl Androl Urol. 2018; 7 (Suppl 3): p.S348-S352.doi: 10.21037/tau.2018.04.11 . | Open in Read by QxMD
  14. Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. Hormone Research in Paediatrics. 2016; 86 (6): p.361-397.doi: 10.1159/000452150 . | Open in Read by QxMD
  15. Gray F, Duyckaerts C, De Girolami U. Escourolle & Poirier's Manual of Basic Neuropathology. Oxford University Press ; 2013
  16. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015

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